Evidence map›Paper›PMID 29688451›Full record

ArticleGigaScience2018

Genome-scale metabolic modeling of responses to polymyxins in Pseudomonas aeruginosa.

Yan Zhu, Tobias Czauderna, Jinxin Zhao, Matthias Klapperstueck, Mohd Hafidz Mahamad Maifiah, Mei-Ling Han, Jing Lu, Björn Sommer, Tony Velkov, Trevor Lithgow and 3 more

Open access · goldAbstract read
In one paragraph

Article in GigaScience, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
2.7field-weighted citation impact, top 9% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

35 citing papers in PubMed, 58 citations in OpenAlex.

  1. Article
  2. Article
  3. Perturbation ofmBio · 2025
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  6. Review
  7. Article
  8. Genomic variations in polymyxin-resistant Pseudomonas aeruginosa clinical isolates and their effects on polymyxin resistance.Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology] · 2023
    Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. Article
  14. Review
  15. A curated collection ofGenome research · 2022
    Article
  16. Dissecting carbon metabolism ofComputational and structural biotechnology journal · 2022
    Article
  17. Article
  18. Review
  19. Frontiers in pharmacology · 2022
    Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 3 institutions in 2 countries.

Yan ZhuMonash Biomedicine Discovery Institute, Department of Microbiology, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne 3800, Australia.
Tobias CzaudernaFaculty of Information Technology, Monash University, Melbourne 3800, Australia.
Jinxin ZhaoMonash Biomedicine Discovery Institute, Department of Microbiology, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne 3800, Australia.
Matthias KlapperstueckFaculty of Information Technology, Monash University, Melbourne 3800, Australia.
Mohd Hafidz Mahamad MaifiahFaculty of Pharmacy and Pharmaceutical Sciences, Monash University, Melbourne 3052, Australia.
Mei-Ling HanFaculty of Pharmacy and Pharmaceutical Sciences, Monash University, Melbourne 3052, Australia.
Jing LuMonash Institute of Cognitive and Clinical Neurosciences, Department of Anatomy and development biology, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne 3800, Australia.
Björn SommerDepartment of Computer and Information Science, University of Konstanz, Konstanz 78457, Germany.
Tony VelkovDepartment of Pharmacology and Therapeutics, University of Melbourne, Melbourne 3010, Australia.
Trevor LithgowMonash Biomedicine Discovery Institute, Department of Microbiology, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne 3800, Australia.
Jiangning SongMonash Biomedicine Discovery Institute, Department of Microbiology, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne 3800, Australia.
Falk SchreiberFaculty of Information Technology, Monash University, Melbourne 3800, Australia.
Jian LiMonash Biomedicine Discovery Institute, Department of Microbiology, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne 3800, Australia.
Monash University · AUUniversity of Konstanz · DEThe University of Melbourne · AU

Funding

New Tricks for 'Old' Drugs: PK/PD of Polymyxin Nonantibiotic CombinationsR01AI111965 · NIAID · MONASH UNIVERSITY · PI LI, JIAN · 2014 to 2018
$4.3M
NIAID NIH HHS R01 AI111965
6 · The paper itself

Abstract

Background: Pseudomonas aeruginosa often causes multidrug-resistant infections in immunocompromised patients, and polymyxins are often used as the last-line therapy. Alarmingly, resistance to polymyxins has been increasingly reported worldwide recently. To rescue this last-resort class of antibiotics, it is necessary to systematically understand how P. aeruginosa alters its metabolism in response to polymyxin treatment, thereby facilitating the development of effective therapies. To this end, a genome-scale metabolic model (GSMM) was used to analyze bacterial metabolic changes at the systems level. Findings: A high-quality GSMM iPAO1 was constructed for P. aeruginosa PAO1 for antimicrobial pharmacological research. Model iPAO1 encompasses an additional periplasmic compartment and contains 3022 metabolites, 4265 reactions, and 1458 genes in total. Growth prediction on 190 carbon and 95 nitrogen sources achieved an accuracy of 89.1%, outperforming all reported P. aeruginosa models. Notably, prediction of the essential genes for growth achieved a high accuracy of 87.9%. Metabolic simulation showed that lipid A modifications associated with polymyxin resistance exert a limited impact on bacterial growth and metabolism but remarkably change the physiochemical properties of the outer membrane. Modeling with transcriptomics constraints revealed a broad range of metabolic responses to polymyxin treatment, including reduced biomass synthesis, upregulated amino acid catabolism, induced flux through the tricarboxylic acid cycle, and increased redox turnover. Conclusions: Overall, iPAO1 represents the most comprehensive GSMM constructed to date for Pseudomonas. It provides a powerful systems pharmacology platform for the elucidation of complex killing mechanisms of antibiotics.

Indexed as

Drug Resistance, BacterialModels, BiologicalAnti-Bacterial AgentsGenome, BacterialPolymyxinsPseudomonas aeruginosaAnti-Bacterial AgentsPolymyxins

Identifiers

PMID29688451
PMCPMC6333913
OpenAlexW2792585663

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.